Ontogenically distinct alveolar macrophages mediate cigarette smoke-induced inflammation and damage

Chronic obstructive pulmonary disease (COPD) is often associated with CS and the third leading cause of death. While airway-recruited macrophages contribute to COPD pathogenesis, the role of embryonic alveolar macrophages (Em-AM) remains unclear.

Using a CS-induced COPD mouse model, we found that CS-triggered lung inflammation and emphysema-like tissue damage correlated with substantial changes in the lung myeloid compartment. Using fate-mapping, we showed that, while most CS-induced AM were recruited bone marrow monocyte-derived AM (BM-AM), Em-AM persisted and underwent similar inflammation- and emphysema-associated adaptations as BM-AM upon CS. Therefore, our data support that the CS-exposed niche, rather than ontogeny, is the main determinant of AM fate in COPD, and that CS-induced AM changes may be potential therapeutic targets to mitigate AM dysfunction in COPD.